Successful immunotherapy against tumors relies in part on the discovery of tumor-specific antigens that are able to stimulate effective immune responses in the host. Several approaches have been developed over the years for the identification of such tumor-specific antigens. The “genetic approach” uses tumor cDNA libraries transfected into target cells expressing appropriate HLA molecules. The “peptide elution approach” uses peptides eluted from tumor HLA and loaded on target cells bearing the same HLA molecules. The “reverse immunology approach” uses peptide sequences derived from already known oncogenes or other putative tumor associated genes that contain desired HLA anchor motifs. All these approaches depend on the availability of tumor-specific T from cancer patients cell lines or clones derived from cancer patients used to recognize the new targets. Most recently, the SEREX approach has been used in which tumor cDNA expression libraries are screened with sera from cancer patients. Existing methods of identifying tumor antigens pose several concerns. For example, many such methods rely on T cells from cancer patients or use tumor cells as antigen presenting cells (APCs). However, T cells from cancer patients often are defective, and tumor cells are often poor APCs (Kiessling et al., Springer Seminars in Immunopathology, 18, 227-42 (1996); Ostrand-Rosenberg, Cur. Opin. Immunol., 6, 722-27 (1994)).
Existing approaches have led to the identification of a panel of tumor antigens (Wang et al., Immunol. Rev. 170, 85-100 (1999)), primarily in melanomas (Boel et al., Immunity, 2, 167-75 (1995); Gaugler et al., J. Exp. Med., 179, 921-30 (1994); Herman et al., Immunogenetics, 43, 377-83 (1996); Traversari et al., J. Exp. Med., 176, 1453-57 (1992); Van den Eynde et al., J. Exp. Med., 182, 689-98 (1995); van der Bruggen et al., Eur. J. Immunol., 24, 3038-43 (1994); van der Bruggen et al., Eur. J. Immunol., 24, 2134-40 (1994)). Very few tumor-specific antigens have been described in epithelial tumors, the best known being the Her-2/neu derived peptides (Disis et al., Crit. Rev. Immunol. 18, 37-45 (1998)) and the core peptides of the MUC-1 tandem repeat (Barratt-Boyes et al., Cancer Immunology, Immunotherapy, 43, 142-51 (1996)).
In light of the foregoing, there remains a need for an improved method for discovering tumor antigens and also for additional tumor antigens.